Contributions
Abstract: PB2037
Type: Publication Only
Background
Myeloproliferative neoplasms (MPN) are characterized by the presence of JAK2V617F mutation that is almost invariably associated with polycythemia vera (PV), but also occurs in the majority of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). JAK2V617F-positive patients display different laboratory and clinical features from JAK2-wild type, but no clear correlation was found between the JAK2V617F allele burden and natural history of the disease. The most common causes of morbidity and mortality in MPN are thrombotic and hemorrhagic complications, albeit bleedings are less frequent than thrombosis and mostly represented by minor hemorrhages (ecchymosis, epistaxis, menorrhagia and gingival hemorrhage). The impact of different allele burden on bleeding risk is uncertain.
Aims
Aim of our study is to explore whether there is an association between JAK2V617F allele burden and hemorrhagic complications in a large cohort of MPN diagnosed and followed in a single center.
Methods
We selected 253 MPN (121 ET= 47.8 %, 124 PV = 49 % and 8 PMF = 3.2 %) carrying JAK2V617F mutation. The median follow-up of patients was 8.8 years (0.1 – 37.3 y). Complete medical history and anti-thrombotic drugs use were recorded. Hemorrhagic complications were classified as “major” or “minor” in agreement with ISTH criteria. The patients were categorized into four groups according to the amount of JAK2 mutant allele, (1st quartile 1-25%, 2nd quartile 26-50%, 3rd quartile 51-75% and 4th quartile 76-100%). Nominal variables were compared with X2 test or Fisher’s exact where indicated. Survival has been evaluated only for groups with different prevalence of events during follow-up and were calculated with the Kaplan Meier method and compared with the Log Rank test.
Results
Three patients (1.2 %) bleed at diagnosis (1 major and 2 minor hemorrhages) while 27 (11.8%) suffered for hemorrhages during follow-up (10 major and 17 minor). Prevalence of hemorrhages results higher in 4th quartile compared both to 2nd (p=0.003) and to 1st (p<0.001) quartiles. Hemorrhages-free survival is confirmed lower in 4th quartile compared both to 2nd (p= 0.004) and to 1st (p<0.001). The incidence rate of hemorrhages are respectively 0.7/100 pats /y for 1st quartile, 0.65/100 pats /y for 2nd quartile, 1.26/100 pats /y for 3rd quartile and 3.23/100 pats /y for 4th quartile with a IRR of 5 and of 4.6 for the 4th quartile respectively versus 2nd and 1st one. No statistically significant difference has been demonstrated in the use of anti-thrombotic drugs among patients of the different quartiles.
Conclusion
Risk factors for hemorrhage in MPN are not well defined, and there is no risk estimation model for this outcome. Acquired von Willebrand disease, entity of platelet increased count and aspirin use have been implicated in bleeding occurrence. Previous reports fail to demonstrate a correlation between JAK2 mutation and bleeding risk. In contrast, in our cohort we found a significantly higher incidence of bleeding manifestations during follow-up in patients with higher allele burden. Interestingly no differences were seen in administration of anti-thrombotic drugs among quartiles, suggesting an independent role of JAK2 allele burden in the different distribution of hemorrhagic events.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Myeloproliferative disorder, Bleeding
Abstract: PB2037
Type: Publication Only
Background
Myeloproliferative neoplasms (MPN) are characterized by the presence of JAK2V617F mutation that is almost invariably associated with polycythemia vera (PV), but also occurs in the majority of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). JAK2V617F-positive patients display different laboratory and clinical features from JAK2-wild type, but no clear correlation was found between the JAK2V617F allele burden and natural history of the disease. The most common causes of morbidity and mortality in MPN are thrombotic and hemorrhagic complications, albeit bleedings are less frequent than thrombosis and mostly represented by minor hemorrhages (ecchymosis, epistaxis, menorrhagia and gingival hemorrhage). The impact of different allele burden on bleeding risk is uncertain.
Aims
Aim of our study is to explore whether there is an association between JAK2V617F allele burden and hemorrhagic complications in a large cohort of MPN diagnosed and followed in a single center.
Methods
We selected 253 MPN (121 ET= 47.8 %, 124 PV = 49 % and 8 PMF = 3.2 %) carrying JAK2V617F mutation. The median follow-up of patients was 8.8 years (0.1 – 37.3 y). Complete medical history and anti-thrombotic drugs use were recorded. Hemorrhagic complications were classified as “major” or “minor” in agreement with ISTH criteria. The patients were categorized into four groups according to the amount of JAK2 mutant allele, (1st quartile 1-25%, 2nd quartile 26-50%, 3rd quartile 51-75% and 4th quartile 76-100%). Nominal variables were compared with X2 test or Fisher’s exact where indicated. Survival has been evaluated only for groups with different prevalence of events during follow-up and were calculated with the Kaplan Meier method and compared with the Log Rank test.
Results
Three patients (1.2 %) bleed at diagnosis (1 major and 2 minor hemorrhages) while 27 (11.8%) suffered for hemorrhages during follow-up (10 major and 17 minor). Prevalence of hemorrhages results higher in 4th quartile compared both to 2nd (p=0.003) and to 1st (p<0.001) quartiles. Hemorrhages-free survival is confirmed lower in 4th quartile compared both to 2nd (p= 0.004) and to 1st (p<0.001). The incidence rate of hemorrhages are respectively 0.7/100 pats /y for 1st quartile, 0.65/100 pats /y for 2nd quartile, 1.26/100 pats /y for 3rd quartile and 3.23/100 pats /y for 4th quartile with a IRR of 5 and of 4.6 for the 4th quartile respectively versus 2nd and 1st one. No statistically significant difference has been demonstrated in the use of anti-thrombotic drugs among patients of the different quartiles.
Conclusion
Risk factors for hemorrhage in MPN are not well defined, and there is no risk estimation model for this outcome. Acquired von Willebrand disease, entity of platelet increased count and aspirin use have been implicated in bleeding occurrence. Previous reports fail to demonstrate a correlation between JAK2 mutation and bleeding risk. In contrast, in our cohort we found a significantly higher incidence of bleeding manifestations during follow-up in patients with higher allele burden. Interestingly no differences were seen in administration of anti-thrombotic drugs among quartiles, suggesting an independent role of JAK2 allele burden in the different distribution of hemorrhagic events.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Myeloproliferative disorder, Bleeding